Scientists in the Institute of Immunology and Immunotherapy at the University of Birmingham have deconstructed the thymus medulla to demonstrate the importance of dendritic cells for immune tolerance.
The immune system operates by discriminating between ‘self’ cells and organs, and ‘non-self’ pathogens, such as viruses and bacteria. T-cells learn this key step in the thymus, the only site in the body that supports T-cell development. When this education process goes wrong, self-reactive T-cells are generated that can cause autoimmune disease. As such, understanding how the thymus selects out harmful T-cells is important in understanding and treating autoimmunity.
In a new study published in the November edition of The Journal of Experimental Medicine, work by Dr Emilie Cosway, Professor Graham Anderson and Dr William Jenkinson examined how the thymus medulla is specialised for T-cell tolerance.
Professor Anderson explained: “The thymus medulla has many features that might explain how it can remove autoreactive T-cells. These include its unique branching structure and the presence of specialised cell types including epithelial and dendritic cells. We wanted to find out which of these features are most important for immune tolerance. This area of research has particular relevance to us, as it was supported by both MRC and the Arthritis Research UK Rheumatoid Arthritis Pathogenesis Centre of Excellence.”
The work of the group involved the deconstruction of the thymus medulla, in which epithelial and dendritic cells and medulla structure were selectively manipulated, to see which components were essential or dispensable for its function.
“We found we could severely disrupt medulla structure, and reduce epithelial cell numbers, without impairing tolerance. However, in experiments where dendritic cells were reduced, autoimmunity occurred. This was surprising as it argues against the long-held view that medulla organisation underpins its function, and instead shows that tolerance thresholds are very sensitive to dendritic cell availability.”
Work in the group is now focussing on how other aspects of thymus function, including the exit of T-cells into peripheral tissues and functionally distinct T-cell types, may also be selectively influenced by particular thymus properties.